PROJECT SUMMARY Type 1 diabetes (T1D), a devastating and expensive organ-specific autoimmune disease once afflicting mainly juveniles, is increasing in incidence among US adults with 40% excess risk of death in women. The long-term objective of this project is to develop a preventive and complementary strategy for T1D management that is non-invasive, long-lasting, and low-cost. Early glycation products (EGPs) generated in the first two steps of Maillard reaction/glycation are proteins modified with reducing sugar moieties, and they are ubiquitous in our daily diet. We successfully produced early glycation products (EGPs) from whey protein isolate (WPI) and glucose using the freeze-drying method, and they were shown to be anti-inflammatory based on functional analysis of cytokines/chemokines produced by macrophages. Further, in a T1D model, the non-obese diabetic (NOD) mouse, we showed that EGPs protected the mice from hyperglycemia with down-regulated CD8+ cells in both thymus and spleen and decreased splenic M1 macrophages. These observations provide preclinical support for the potential nutraceutical application of EGPs for patients with insulitis and T1D (e.g., medical food). For the large-scale production of EGPs, the spray-drying method is more appropriate due to its energy efficiencies and enhanced product and process flexibility. However, the parameters for spray drying and the anti-hyperglycemia effects of the spray dried products remained unknown. The proposed research in phase I will focus on (Aim 1) testing whether the EGPs produced using the spray drying method exert a similar protection in T1D and (Aim 2) on testing that the uptake of EGPs has no adverse effects in host resistance mechanisms. HGG Research LLC is a company that will generate EGPs by optimizing the parameters of spray drying for their production. Research by the academic partner, currently at the University of Georgia, will evaluate the T1D prevention and toxicity following EGP uptake. Next, it would be a logical extension to determine the effects of EGPs on T1D prevention using other models (e.g., Biobreeding diabetes-prone rat) and the underlying mechanisms (e.g.,microbiome), andinvestigate which EGP component(s) are active in this indication. Reversing autoimmunity could be beneficial well beyond subjects with T1D. The design of studies to test other autoimmune diseases such as Crohn's, rheumatoid arthritis and lupus erythematous would be the next stage following this STTR project. We believe that the proposed research is innovative and of great significance; and represents a frontier in health care and research.